HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Herbert, J.-M. Articles by Carmeliet, P. Search for Related Content PubMed PubMed Citation Articles by Herbert, J.-M. Articles by Carmeliet, P. Social Bookmarking                      What's this?

Volume 272, Number 38, Issue of September 19, 1997 pp. 23585-23591
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Urokinase and Tissue-type Plasminogen Activator Are Required for the Mitogenic and Chemotactic Effects of Bovine Fibroblast Growth Factor and Platelet-derived Growth Factor-BB for Vascular Smooth Muscle Cells

(Received for publication, February 26, 1997, and in revised form, July 9, 1997)

From the Haemobiology Research Department, Sanofi Recherche, 31036 Toulouse, France and the ^§ Center for Transgene Technology and Gene Therapy, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

The present study was undertaken to evaluate in vitro the relative importance of tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) in the mitogenic and chemotactic potential of bovine fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF)-BB for smooth muscle cells (SMC). Aortic SMC were isolated from transgenic mice showing single inactivations of the t-PA, u-PA, plasminogen activator inhibitor-1, or urokinase-type plasminogen activator receptor (u-PAR) genes. With regard to serum-induced proliferation, all cell types showed similar responses. However, SMC isolated from t-PA-deficient mice did not proliferate or migrate in response to PDGF, whereas SMC isolated from u-PA-deficient animals appeared to be much less sensitive to bFGF than the cells isolated from the other animals. Supplementation of cells from deficient animals with exogenous murine t-PA or u-PA restored the normal response of the growth factors with regard to both migration and proliferation. The mitogenic and chemotactic responses of bFGF were specifically inhibited in u-PAR-deficient cells or in wild-type SMC, cultured in the presence of antibodies to u-PAR. The role of u-PA and t-PA in bFGF and PDGF-induced growth and migration of SMC was not dependent on plasmin generation and activity as demonstrated by the inactivity of -aminocaproic acid and aprotinin. A 4-5-fold increase in the steady-state levels of u-PA and t-PA mRNA and proteins were observed after 24 h of incubation of the cell cultures with bFGF and PDGF-BB, respectively. These results therefore indicate that, at least in vitro, t-PA is an important element of the activity of PDGF-BB with regard to the proliferation and migration of SMC whereas u-PA is a key factor in the effect of bFGF on SMC.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				W. T. Gerthoffer Mechanisms of Vascular Smooth Muscle Cell Migration Circ. Res., March 16, 2007; 100(5): 607 - 621. [Abstract] [Full Text] [PDF]

				H. Bujo and Y. Saito Modulation of Smooth Muscle Cell Migration by Members of the Low-Density Lipoprotein Receptor Family Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1246 - 1252. [Abstract] [Full Text] [PDF]

				M. Jinnin, H. Ihn, and K. Tamaki Characterization of SIS3, a Novel Specific Inhibitor of Smad3, and Its Effect on Transforming Growth Factor-beta1-Induced Extracellular Matrix Expression Mol. Pharmacol., February 1, 2006; 69(2): 597 - 607. [Abstract] [Full Text] [PDF]

				M.L.M. Lamfers, J.M. Grimbergen, M.C. Aalders, M.J. Havenga, M.R. de Vries, L.G.M. Huisman, V.W.M. van Hinsbergh, and P.H.A. Quax Gene Transfer of the Urokinase-Type Plasminogen Activator Receptor-Targeted Matrix Metalloproteinase Inhibitor TIMP-1.ATF Suppresses Neointima Formation More Efficiently Than Tissue Inhibitor of Metalloproteinase-1 Circ. Res., November 15, 2002; 91(10): 945 - 952. [Abstract] [Full Text] [PDF]

				T. Padro, R. M. Mesters, B. Dankbar, H. Hintelmann, R. Bieker, M. Kiehl, W. E. Berdel, and J. Kienast The catalytic domain of endogenous urokinase-type plasminogen activator is required for the mitogenic activity of platelet-derived and basic fibroblast growth factors in human vascular smooth muscle cells J. Cell Sci., January 5, 2002; 115(9): 1961 - 1971. [Abstract] [Full Text] [PDF]

				B. Degryse, M. Resnati, S. A. Rabbani, A. Villa, F. Fazioli, and F. Blasi Src-Dependence and Pertussis-Toxin Sensitivity of Urokinase Receptor-Dependent Chemotaxis and Cytoskeleton Reorganization in Rat Smooth Muscle Cells Blood, July 15, 1999; 94(2): 649 - 662. [Abstract] [Full Text] [PDF]

				G. W. Hoyle, J. Li, J. B. Finkelstein, T. Eisenberg, J.-Y. Liu, J. A. Lasky, G. Athas, G. F. Morris, and A. R. Brody Emphysematous Lesions, Inflammation, and Fibrosis in the Lungs of Transgenic Mice Overexpressing Platelet-Derived Growth Factor Am. J. Pathol., June 1, 1999; 154(6): 1763 - 1775. [Abstract] [Full Text] [PDF]

				T. M. Saxton and T. Pawson Morphogenetic movements at gastrulation require the SH2 tyrosine phosphatase Shp2 PNAS, March 30, 1999; 96(7): 3790 - 3795. [Abstract] [Full Text] [PDF]

				M.-L. Bochaton-Piallat, G. Gabbiani, and M. S. Pepper Plasminogen Activator Expression in Rat Arterial Smooth Muscle Cells Depends on Their Phenotype and Is Modulated by Cytokines Circ. Res., June 1, 1998; 82(10): 1086 - 1093. [Abstract] [Full Text] [PDF]

				S. Mukhina, V. Stepanova, D. Traktouev, A. Poliakov, R. Beabealashvilly, Y. Gursky, M. Minashkin, A. Shevelev, and V. Tkachuk The Chemotactic Action of Urokinase on Smooth Muscle Cells Is Dependent on Its Kringle Domain. CHARACTERIZATION OF INTERACTIONS AND CONTRIBUTION TO CHEMOTAXIS J. Biol. Chem., May 26, 2000; 275(22): 16450 - 16458. [Abstract] [Full Text] [PDF]